Study of TAK-559 in Treating Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria:

• Had type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, currently treated with insulin therapy.
• Required sponsor approval if older than 65 years.
• Had a Screening glycosylated hemoglobin less than or equal to 8.0%.
• Had a Screening fasting plasma glucose less than or equal to 200 mg/dL (11.1 mmol/L).
• Had a Screening low density lipoprotein less than or equal to 160 mg/dL (4.1 mmol/L).
• Had a Screening thyroid stimulating hormone level less than or equal to 5.5 μU/mL (5.5 μU/L) and greater than or equal to 0.35 μU/mL (0.35 μU/L).
• Was willing to continue dietary counseling during study and had dietary advice greater than or equal to 2.5 months prior to Screening.
• Had a Screening ejection fraction greater than or equal to 40% from echocardiogram.
• Had a Screening blood pressure less than or equal to 140/95 mm Hg.
• Was willing to perform daily self-monitoring blood glucose tests.
• A female subject of childbearing potential who was sexually active agreed to use adequate contraception, and was neither pregnant nor lactating from Screening throughout the duration of the study.
• Was in good health as determined by physician (via medical history and physical examination) other than having type 2 diabetes mellitus.
• Had clinical laboratory evaluations within normal reference range or deemed not clinically significant by the investigator or sponsor.
• Started insulin therapy at least 3 months prior to Randomization.

Exclusion Criteria:

• Had a hypersensitivity to peroxisome proliferator-activated receptor -alpha or gamma agonists, thiazolidinediones, or fibrates.
• Was diagnosed with type 1 diabetes mellitus or hemochromatosis, or had a history of ketoacidosis.
• Required greater than 2 hypertension medications to achieve adequate blood pressure control.
• Had a history of coronary angioplasty or bypass graft, or unstable angina pectoris within 1 year of Screening.
• Had a history of myocardial infarction.
• Had a history of transient ischemic attack or documented cerebrovascular accident within 6 months of Screening.
• Abdominal, thoracic, or vascular surgery within 6 months of Screening warranting exclusion (investigator's opinion).
• Had a screening creatine phosphokinase value greater than 3 times the upper limit of normal.
• Had persistent unexplained microscopic or macroscopic hematuria or history of bladder cancer.
• Had a screening triglyceride level greater than 500 mg/dL (5.6 mmol/L).
• Experienced a change in allowed lipid-lowering medication (dose or drug) within 2 months of Randomization.
• Experienced a change in blood pressure medication (dose or drug) within 1 month of Randomization.
• Had systemic corticosteroids within 1 month of Randomization.
• Had donated or received blood products within 3 months of Randomization.
• Had a condition known to invalidate glycosylated hemoglobin.
• Had a history of drug abuse or alcohol abuse within 2 years.
• Had a significant cardiovascular disease, including New York Heart Association Functional (Cardiac) Classification II, III or IV.
• Had a Screening B-Type Natriuretic Peptide greater than 100 pg/mL (100 ng/L).
• Had a history of left ventricular hypertrophy (women greater than 110 g/m2 and men greater than 134 g/m2).
• Had a clinically significant mitral insufficiency at Screening.
• Had a clinically significant aortic stenosis at Screening.
• Had a Screening body mass index greater than 45.
• Had a history of cancer with no remission within 5 years of Randomization, other than basal cell or stage 1 squamous cell carcinoma of the skin.
• Had an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease or jaundice at Screening.
• Had a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening.

• Was required to take or intended to continue taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfered with the evaluation of the study medication, including:

  • oral antidiabetic agents (including sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, peroxisome proliferator-activated receptor agonists and metformin)
  • fibrates
  • systemic corticosteroids
  • warfarin
  • rifampin
  • nicotinic acid
  • minoxidil
  • hydralazine
  • St. John's Wort
• Was participating or had participated in an investigational study within the past 30 days.
• Had a serious disease or condition at Screening or Randomization that could affect life expectancy or made it difficult to manage/follow patient according to protocol.